PINK1 controls mitochondrial localization of Parkin through direct phosphorylation.
PTEN-induced putative kinase 1 (PINK1) and Parkin, encoded by their respective genes associated with Parkinson's disease (PD), are linked in a common pathway involved in the protection of mitochondrial integrity and function. However, the mechanism of their interaction at the biochemical level has not been investigated yet. Using both mammalian and Drosophila systems, we here demonstrate that the PINK1 kinase activity is required for its function in mitochondria. PINK1 regulates the localization of Parkin to the mitochondria in its kinase activity-dependent manner. In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. These results demonstrate the biochemical relationship between PINK1, Parkin, and the mitochondria and thereby suggest the possible mechanism of PINK-Parkin-associated PD pathogenesis.
Kim
Yongsung
Y
National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-Dong, Yusong-Gu, Taejon 305-701, Republic of Korea.
Park
Jeehye
J
Kim
Sunhong
S
Song
Saera
S
Kwon
Seok-Kyu
SK
Lee
Sang-Hee
SH
Kitada
Tohru
T
Kim
Jin-Man
JM
Chung
Jongkyeong
J
D000818:Animals; D002460:Cell Line; D004331:Drosophila melanogaster / Q000201:enzymology; D006801:Humans; D008931:Mitochondria, Muscle / Q000201:enzymology*; D010300:Parkinson Disease / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein